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To the Editor:Cardiac resynchronization therapy (CRT) improves symptoms and decreases hospitalizations in selected patients with heart failure (1,2). With CRT, pacing from the left ventricle (LV) alters the ventricular activation (VA) sequence, changing the QRS morphology. In responders, change in VA improves cardiac filling and ejection (3). However, many patients are nonresponders. The LV lead location is the major determinant of paced activation but is often constrained by the location of coronary sinus vein branches. During LV mapping for ventricular tachycardia, increased pacing stimulus strength (SS) has been demonstrated to capture an enlarged myocardial area, producing a larger “virtual electrode” (4). If the enlarged area of myocardial capture extends beyond a discrete region of conduction block, the SS increase could result in VA change and more rapid conduction to a remote location, such as the right ventricular (RV) apex.

We hypothesized that paced VA can be manipulated by increasing SS. We expected activation changes to be more marked when pacing near areas of scarred or infarcted myocardium.

Using an electroanatomic mapping system (CARTO, Biosense-Webster Inc., Diamond Bar, California), three-dimensional plots (mean of 136 ± 47 points per patient) of bipolar electrogram amplitude were created (5). Endocardial LV mapping was performed with a 7-F steerable catheter (Biosense-Webster Inc.). Electrograms were recorded on a separate digital system (Prucka Engineering Inc., Houston, Texas). Epicardial mapping by percutaneous subxiphoid approach was performed in one patient. Catheter stability was confirmed by biplane fluoroscopy, the mapping system, and continuous monitoring of electrogram morphology and timing.

Pacing at outputs of threshold, 5 mA, and 10 mA was performed at 6 to 10 separated LV sites. In one case, epicardial pacing at 20 mA was performed because of high pacing threshold (10 mA). The anode was in the inferior vena cava (IVC). A quadripolar catheter at the RV apex was the reference catheter. Atrial, ventricular, and His bundle electrograms were assessed to exclude antegrade atrial conduction during pacing.

Stimulus to RV conduction times and stimulus to QRS conduction times (QRS latency) were measured from the stimulus artifact to the first bipolar peak of the electrogram from the RV apical catheter and to the earliest VA in the surface electrocardiogram (ECG). Changes in QRS morphology with pacing were defined as any of the following: QRS width change of >40 ms; new Q-, R-, or S-wave of >25% of the total QRS amplitude; >50% change in ratio of R or S components of QRS complex; precordial transition change of more than one lead; >30° change in QRS axis (6).

Ventricular activation indices were analyzed at threshold and at 10 mA of current output. Comparisons of continuous, paired data were made using paired ttests. Where appropriate, results were adjusted using repeated measures analysis of variance to account for multiple observations in individual patients. A p value of <0.05 was considered significant. Analysis was conducted using SAS software (Version 8.2, SAS Institute Inc., Cary, North Carolina).

(A)Endocardial bipolar electroanatomic map of the left ventricle (LV). Normal voltage areas are purple, and electrogram amplitude progressively diminishes as colors proceed to blue, green, yellow, and red. Unexcitable scar with pacing threshold >10 mA is gray(4). There is a large anteroapical scar (gray). The yellow arrow and dotindicate the site of pacing near the apex. (B)Paced 12-lead electrocardiograms during threshold (left)and 10 mA high-output pacing (right)at the site indicated in panel A. The initial R-wave in V3and V4increases with high output pacing. (C)Corresponding intracardiac signals from the right ventricle apex (RVA) and five electrocardiogram (ECG) leads. Threshold pacing is shown on the left; high-output pacing, on the right. The stimulus to RVA electrogram time shortens from 275 to 199 ms with increase in stimulus strength. (D)Epicardial bipolar electroanatomic map of the LV. The yellow arrow and dotindicate the pacing site at the basal free wall of the LV, between two small areas of unexcitable scar (gray). (E)12-lead ECGs during pacing at threshold (left)and 20 mA high-output pacing (right)at the site shown in panel A. In leads V3through V6, an increase in R-wave occurs with high-output pacing. (F)Intracardiac signal from the RVA and five ECG leads. Threshold pacing is shown on the left; high output pacing, on the right. The stimulus to RVA electrogram time shortens from 392 to 208 ms with increase in stimulus strength. Continued on next page.

Increasing SS during LV pacing reduces conduction time from the LV to the RV and can produce a sufficient change in VA to produce a change in QRS morphology. These findings are consistent with an increase in virtual electrode size as SS is increased. The effect appears most marked in low-amplitude regions, such as infarct borders (5). Although QRS duration and magnitude of reduction in QRS duration may not reliably correlate with response to CRT (7), VA change is necessary for successful resynchronization. Anatomic constraints in lead position may result in failure to respond to CRT (3). Our findings indicate that SS can be manipulated to influence VA. Potentially, resultant changes in QRS latency and morphology could be used to influence paced interventricular and intraventricular delays during CRT.

Potential limitations of application to CRT include phrenic nerve capture at high SS and shortened device battery life. Study limitations include a small patient number and a potential selection bias of electroanatomic mapping points during ablation. Pacing was endocardial in all but one patient, but epicardial pacing in one patient demonstrated similar VA parameter decreases with QRS morphology changes at three of eight pacing sites. We used unipolar pacing with an anode in the IVC to eliminate the confounding effects of anodal capture, whereas the anode in CRT devices is at the ring of the RV apical lead. The impact of SS when using current CRT systems requires further investigation with hemodynamic correlation.

Increases in SS can change paced VA. The changes can be marked and are more likely to occur in abnormal areas associated with scar or infarction that are marked by low electrogram voltage. Manipulation of the virtual electrode by altering SS may provide a simple means of adjusting CRT.

Footnotes

↵1 Please note: Drs. Stevenson and Soejima have participated in corporate-sponsored research for Biosense-Webster, which initially developed the electroanatomic mapping system which was used in this study.

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